title: Aβ increases neural stem cell activity in senescence-accelerated SAMP8 mice.
abstract: Neurogenesis persists in the adult brain as a form of plasticity due to the existence of neural stem cells (NSCs). Alterations in neurogenesis have been found in transgenic Alzheimer's disease (AD) mouse models, but NSC activity and neurogenesis in sporadic AD models remains to be examined. We herein describe a remarkable increase in NSC proliferation in the forebrain of SAMP8, a non-transgenic mouse strain that recapitulates the transition from healthy aging to AD. The increase in proliferation is transient, precedes AD-like symptoms such as amyloid beta 1-42 [Aβ(1-42)] increase or gliosis, and is followed by a steep decline at later stages. Interestingly, in vitro studies indicate that secreted Aβ(1-42) and PI3K signaling may account for the early boost in NSC proliferation. Our results highlight the role of soluble Aβ(1-42) peptide and PI3K in the autocrine regulation of NSCs, and further suggest that over-proliferation of NSCs before the appearance of AD pathology may underlie neurogenic failure during the age-related progression of the disease. These findings have implications for therapeutic approaches based on neurogenesis in AD.
authors.affiliation: Unidad de Neurobiología Molecular, Área de Biología Celular y Desarrollo, UFIEC, Instituto de Salud Carlos III, Majadahonda, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Díaz-Moreno
authors.forename: Rafael
authors.initials: R
authors.lastname: Hortigüela
authors.forename: Ania
authors.initials: A
authors.lastname: Gonçalves
authors.forename: Irmina
authors.initials: I
authors.lastname: García-Carpio
authors.forename: Gemma
authors.initials: G
authors.lastname: Manich
authors.forename: Edurne
authors.initials: E
authors.lastname: García-Bermúdez
authors.forename: Mireia
authors.initials: M
authors.lastname: Moreno-Estellés
authors.forename: César
authors.initials: C
authors.lastname: Eguiluz
authors.forename: Jordi
authors.initials: J
authors.lastname: Vilaplana
authors.forename: Carme
authors.initials: C
authors.lastname: Pelegrí
authors.forename: Marçal
authors.initials: M
authors.lastname: Vilar
authors.forename: Helena
authors.initials: H
authors.lastname: Mira
mesh_terms: D053687:Adult Stem Cells / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D000367:Age Factors; D000375:Aging / Q000235:genetics* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D018949:Antigens, CD1; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C075222:amyloid beta-protein (1-42); D019869:Phosphatidylinositol 3-Kinases; D001973:Bromodeoxyuridine
keywords: Alzheimer's disease; Amyloid beta; Neural stem cell; Neurogenesis; Neurosphere; Olfactory bulb; SAMP8; Senescence-accelerated mouse; Subventricular zone